(A) Published European Patent Application No. 30,630 discloses a vast number of 7-acylamino-3-vinylcephalosporanic acid derivatives including, inter alia, those of the formula ##STR4## wherein R inter alia may be (lower)alkyl, (lower)alkenyl, (lower)alkynyl or carboxy(lower)alkyl. The compounds are prepared, inter alia, by reaction of the corresponding 3-halomethyl compound with a triarylphosphine, followed by treatment with a base and reaction with formaldehyde. In each case, the final 3-substituent is the vinyl group. There is no disclosure or suggestion of a quaternary ammonio-substituted propenyl moiety for the 3-substituent.
(B) U.K. Patent Specification No. 1,399,086 contains a generic disclosure encompassing a vast number of cephalosporins of the formula ##STR5## wherein R is hydrogen or an organic group, R.sup.a is an etherifying monovalent organic group linked to the oxygen through a carbon atom, B is &gt;S or &gt;S.fwdarw.O, and P is an organic group. In one embodiment, P may be inter alia a vinyl group of the formula ##STR6## in which R.sup.3 and R.sup.4 independently may be hydrogen, nitrile, (lower)alkoxycarbonyl, or substituted or unsubstituted aliphatic, cycloaliphatic, araliphatic or aromatic. However, the 2-aminothiazol-4-yl group is not identified as a possible R substituent and there is no disclosure or suggestion that P may be a quaternary ammonio-substituted propenyl group. U.S. Pat. No. 3,971,778 and its divisionals U.S. Pat. Nos. 4,024,133, 4,024,137, 4,064,346, 4,033,950, 4,079,178, 4,091,209, 4,092,477 and 4,093,803 have similar disclosures.
(C) U.S. Pat. No. 4,307,233 discloses, inter alia, 3-vinyl cephalosporin derivatives of the formula ##STR7## in which R.sup.5 inter alia may be alkyl, vinyl, cyanomethyl or a protective group such as 2-methoxyprop-2-yl, and R.sup.3 and R.sup.4 are alkyl groups (optionally substituted by hydroxy, alkoxy, amino, alkylamino or dialkylamino) or phenyl groups, or R.sup.3 and R.sup.4, taken together with the nitrogen to which they are attached, may form a saturated heterocyclic ring of 5 or 6 members, optionally containing another hetero-atom selected from N, O and S, and optionally substituted by an alkyl group. The compounds are useful as intermediates in the preparation of 3-thiovinyl cephalosporin derivatives. There is no disclosure or suggestion of a quaternary ammonio-substituted propenyl moiety for the 3-substituent. Published United Kingdom Patent Application No. 2,051,062 is concordant thereto and has a similar disclosure.
(D) Published European Patent Application No. 53,537 discloses, inter alia, 3-vinylcephalosporin derivatives of the formula ##STR8## in which R.sub.5.sup.a and R.sub.5.sup.b are the same or different and are hydrogen or alkyl, or taken together, form an alkylene group containing 2 or 3 carbon atoms, R.sub.5.sup.c is an acid protecting group, R.sub.2 is an acid protecting group such as an ester, R.sub.3 and R.sub.4 are the same or different and are hydrogen, alkyl (optionally substituted by hydroxy, alkoxy, amino, alkylamino or dialkylamino) or phenyl groups, or R.sub.3 and R.sub.4, taken together with the nitrogen to which they are attached, may form a saturated heterocyclic ring of 5 or 6 members, optionally containing another hetero-atom selected from N, O and S, and optionally substituted by an alkyl group. The compounds are useful as intermediates in the preparation of 3-thiovinyl cephalosporin derivatives. There is no disclosure or suggestion of a quaternary ammonio-substituted propenyl group for the 3-substituent.
(E) U.S. Pat. No. 4,307,116 discloses 3-thiovinylcephalosporins of the formula ##STR9## in which R.degree. is hydrogen, alkyl, vinyl or cyanomethyl, and R inter alia may be one of a vast number of heterocyclic rings such as ##STR10## or the like. However, in each case, the heterocyclic ring is attached to the sulfur atom via a carbon atom of the heterocyclic ring. There is no disclosure or suggestion of a quaternary ammonio-substituted propenyl moiety for the 3-substituent. Although not formally related, published European Patent Application No. 53,961 has a similar disclosure, but includes 2-carboxyprop-2-yl, 1-carboxycyclobut-1-yl and the like as possible meanings of R.degree..
(F) Published European Patent Application No. 53,074 generically discloses a vast number of 3-vinylcephalosporin derivatives of the formula ##STR11## wherein R.degree..sub.1a (in one of several embodiments) may be ##STR12## in which R.sub.5 inter alia may be hydrogen, alkyl, vinyl, cyanomethyl, an oxime-protecting group such as trityl, etc., or a group of the formula ##STR13## in which R.sup.a.sub.5 and R.sup.b.sub.5 are the same or different, and may be hydrogen, alkyl or, taken together, an alkylene radical of 2 or 3 carbon atoms, and R.sup.c.sub.5 is hydrogen or an acid-protecting radical; R.degree..sub.2a is hydrogen or an acid-protecting radical such as methoxy-methyl; R.degree. (in one of several embodiments) may be a methyl group substituted by a 5- or 6-membered atomatic heterocyclic ring containing a single hetero atom, such as 2- or 3-pyridyl, or 2- or 3-thienyl or 2- or 3-furyl; and R.sub.3 is a group of the formula ##STR14## in which R.sub.4 may be alkyl, trihalomethyl or optionally substituted phenyl.
These compounds are stated to be intermediates in the preparation of compounds in which the 3-substituent is a group of the formula ##STR15## which are stated to have antibacterial activity.
Although this patent includes the possibility of R.degree. being a methyl group substituted by an N-containing heterocyclic ring, in both the intermediates and final products (thus giving a heterocyclic-substituted propenyl moiety), it teaches only that the heterocyclic ring is attached via one of its carbon atoms. Thus, there is no suggestion of a quaternary ammonio-substituted propenyl group. The reference exemplifies R.degree. in the intermediates and final products only as methyl. Further, in both the intermediates and final product, the propenyl group must contain a second substituent (--O.sub.3 SR.sup.4 or --SR, respectively).
(G) Published European Patent Application No. 53,538 discloses, inter alia, 3-vinylcephalosporin intermediates of the formula ##STR16## in which n is 0 or 1, R.sup.5 is hydrogen, alkyl, vinyl, cyanomethyl or an oxime-protecting group, and R.sup.3 is halogen.